The major cause of death in cancer patients with solid tumors is the recurrence of the cancer after surgery as multiple metastases that are nonresectable and/or refractory to any therapy. The majority of these patients are considered to have a terminal cancer disease. As no treatment is available for them, many of these patients die within weeks or few months after detection of metastatic tumor lesions.
Tumors develop in cancer patients because the immune system fails to detect tumor cells as cells that ought to be destroyed. Tumor cells express autologous tumor antigens in a large proportion of cancer patients. These autologous tumor antigens may elicit a protective anti-tumor immune response. Tumor cells, or tumor cell membranes, have to be internalized by antigen presenting cells in order to induce the development of an anti-tumor immune response. However, the immune system in cancer patients displays “ignorance” toward the tumor antigens that is associated with early development of the tumor in a “stealthy” way, so it is “invisible” to antigen presenting cells (Pardoll D M. 2000; Clin Immunol. 95:S44-49, and Dunn G P, Bruce A T, Ikeda H, Old L J, Schreiber R D. Nat Immunol 2002; 3: 991-8).
In addition, the tumor microenvironment and local cytokine milieu are often suppressive toward immune function and can actively induce immune cell anergy and death (Malmberg K J. Cancer Immunol Immunother. 2004; 53: 879-92; Lugade A A, Moran J P, Gerber S A, Rose R C, Frelinger J G, Lord E M. J Immunol. 2005; 174: 7516-23). Effective treatment of such metastatic tumor lesions requires two components:                1. Destruction of the lesions that are large enough to be detected visually or by imaging technology, and        2. Induction of a protective anti-tumor immune response against tumor antigens.Such an immune response results in immune mediated detection, regression, and/or destruction of micrometastases which can not be detected visually and are not detectable by imaging.        
Induction of a protective anti-tumor immune response requires uptake of the tumor cells or cell membranes by antigen presenting cells and their transportation to the draining lymph nodes, where the antigen presenting cells process the tumor antigen molecules. The immunogenic tumor antigen peptides are presented by antigen presenting cells in association with class I or class II MHC molecules for the activation of tumor specific CD8+ and CD4+ T cells, respectively. Only after these T cells are activated by the processed and presented tumor antigen peptides, these lymphocytes can leave the lymph nodes, circulate in the body, seek and destroy metastatic tumor cells expressing tumor antigens. In addition, only after they are activated, helper T cells can provide help to B cells for producing antibodies against the tumor antigens. However, since the tumor cells naturally evolve to be “invisible” to antigen presenting cells, the developing tumor metastases are usually ignored by the immune system to the extent that metastasizing tumor cells can proliferate even within lymph nodes. Therefore, eliciting an effective anti-tumor immune response requires effective targeting of tumor cells to antigen presenting cells.
What is needed in the art are compositions and methods to non-surgically introduce compounds into a solid tumor under conditions such that a naturally occurring antibody will interact with the introduced compound. Such interaction will induce local inflammation for the regression and/or destruction of the tumor and the targeting tumor cells and/or tumor cell membranes to antigen presenting cells. This process elicits a protective immune response in the host against tumor antigens on tumor cells in micrometastases that can not be detected visually or by imaging and therefore can not be removed by resection.